In recent years, scientific evidence proving the inadequacy of monolayer cell cultures have triggered the development of techniques that allow culturing of cells in a three-dimensional (3D) environment. These techniques include the use of suitable porous biomaterials, i.e. scaffolds, that can be seeded with cells but can also include cell clusters, tissue or tissue like structures, biopsies and similar.
As a consequence, tools have been made available to respond to specific needs inherent to these techniques. Among these tools, bioreactors provide a controlled chemo-physical environment suitable for the culturing of cells in 3D. In particular, perfusion bioreactors have proven to be effective in overcoming typical limitations of static cultures. Such limitations include lack of a uniform cell seeding through the scaffold, limited mass transport, i.e. nutrient delivery and waste removal, particularly in a central part of the scaffold.
For example, in the article “Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tension” of Wendt D. et al. from the Departments of Surgery and of Research of the University Hospital Basel, Switzerland, published in Biorheology, 43, 481-488, 2006, a bioreactor for 3D cell culturing is shown. This bioreactor comprises a first tube and a second tube each being connected to a scaffold chamber via a three way valve. The first tube is made of Teflon and provided with a cell suspension. The second tube comprises a portion made of Teflon and a flexible portion. The first tube and the flexible portion of the second tube are connected to a pump allowing to circulate the cell suspension through the scaffold chamber in which a porous scaffold is arranged. The three way valves are additionally connected to the pump and a medium storage. The valves are further arranged to be in medium change position in which the first and second tubes are in fluid connection with the medium storage and an operation position in which the first and second tubes are connected to the scaffold chamber.
However, such bioreactors are usually comparably cumbersome to set up and to operate such that mistakes impairing cell culturing can occur. For example, when setting up such a bioreactor numerous components of various vendors have to be manually assembled wherein these components frequently do not properly fit together. Further, such bioreactors are typically made of comparably expensive recyclable components that are used for multiple cycles which bears the risk of accumulation of undesired substances. Still further, the three way valves used within such bioreactors usually have to be operated by rotating an actuator in various proper rotational positions. Operation of these three way valves often is confusing and can easily induce mistakes when being handled particularly by inexperienced users.
Therefore, there is a need for a bioreactor and system allowing for a convenient operation and handling within cell culturing.